Replication Data for: High resolution daily profiles of tissue adrenal steroids by portable automated collection

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Upton, Thomas; Zavala, Eder; Methlie, Paal; Kämpe, Olle; Tsagarakis, Stylianos; Øksnes, Marianne; Bensing, Sophie; Vassiliadi, Dimitra; Grytaas, Marianne; Botusan, Ileana; Ueland, Greta; Berinder, Katerina; Simunkova, Katerina; Balomenaki, Maria; Margaritopoulos, Dimitris; Henne, Nina; Crossley, Robin; Russell, Georgina; Husebye, Eystein; Lightman, Stafford, 2023, "Replication Data for: High resolution daily profiles of tissue adrenal steroids by portable automated collection", https://doi.org/10.18710/5TW8YF, DataverseNO, V1

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Description	1. Time series measurements of adrenal hormones, measured in microdialysis fluid 2. Time series measurements of adrenal hormones and ACTH, measured in blood plasma 3. Supporting metadata 4. Non-validated questionnaire responses Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of disease. Since adrenal hormones are secreted with both circadian and ultradian periods, conventional single time point measures provide limited information about rhythmicity, and crucially do not provide information during sleep when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, this necessitates admission to a clinical research unit, can be stressful and disturbs sleep. To overcome this problem, and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector and liquid-chromatography tandem mass-spectrometry (LC-MS/MS) to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone (CCS), 18-hydroxycortisol (18-OHF), aldosterone, tetrahydrocortisol (THF), allotetrahydrocortisol (aTHF), and the presence of dehydroepiandrosterone sulphate (DHEA-S). We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop “dynamic biomarkers” of normality in healthy individuals stratified by sex, age and body mass index (BMI). Our results provide, for the first time, an insight into the dynamics of adrenal steroids in tissue in real world settings and will serve as a normative reference for novel and improved biomarkers of endocrine disorders. (ULTRADIAN, NCT02934399).
Subject	Medicine, Health and Life Sciences
Keyword	Microdialysis, Monitoring, Ambulatory, Tandem Mass Spectrometry, Adrenal Cortex Function Tests, Biomedical Technology, Ultradian Rhythm, Circadian Rhythm, Adrenal Gland Diseases, Adrenal Cortex Hormones, Hydroxycorticosteroids
Related Publication	Upton TJ, Zavala E, Methlie P, Kämpe O, Tsagarakis S, Øksnes M, et al. High-resolution daily profiles of tissue adrenal steroids by portable automated collection. Science Translational Medicine. 2023;15(701):eadg8464. doi: 10.1126/scitranslmed.adg8464
License/Data Use Agreement	CC0 1.0

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Citation Metadata

Persistent Identifier	doi:10.18710/5TW8YF
Publication Date	2023-06-21
Title	Replication Data for: High resolution daily profiles of tissue adrenal steroids by portable automated collection
Author	Upton, Thomas (University of Bristol) - ORCID: 0000-0003-0138-3982 Zavala, Eder (University of Birmingham) - ORCID: 0000-0002-5467-6036 Methlie, Paal (University of Bergen) - ORCID: 0000-0003-0548-0034 Kämpe, Olle (Karolinska Institute) Tsagarakis, Stylianos (Geniko Nosokomeio Athenon O Euangelismos) Øksnes, Marianne (University of Bergen) Bensing, Sophie (Karolinska Institute) Vassiliadi, Dimitra (Evangelismos General Hospital) Grytaas, Marianne (Haukeland University Hospital) Botusan, Ileana (Karolinska Institute) Ueland, Greta (Haukeland University Hospital) Berinder, Katerina (Karolinska Institute) Simunkova, Katerina (University of Bergen) Balomenaki, Maria (Evangelismos General Hospital) Margaritopoulos, Dimitris (Evangelismos General Hospital) Henne, Nina (University of Bergen) Crossley, Robin (Designworks Windsor) Russell, Georgina (University of Bristol) Husebye, Eystein (University of Bergen) Lightman, Stafford (University of Bristol)
Point of Contact	Use email button above to contact. Upton, Thomas (University of Bristol)
Description	1. Time series measurements of adrenal hormones, measured in microdialysis fluid 2. Time series measurements of adrenal hormones and ACTH, measured in blood plasma 3. Supporting metadata 4. Non-validated questionnaire responses Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of disease. Since adrenal hormones are secreted with both circadian and ultradian periods, conventional single time point measures provide limited information about rhythmicity, and crucially do not provide information during sleep when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, this necessitates admission to a clinical research unit, can be stressful and disturbs sleep. To overcome this problem, and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector and liquid-chromatography tandem mass-spectrometry (LC-MS/MS) to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone (CCS), 18-hydroxycortisol (18-OHF), aldosterone, tetrahydrocortisol (THF), allotetrahydrocortisol (aTHF), and the presence of dehydroepiandrosterone sulphate (DHEA-S). We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop “dynamic biomarkers” of normality in healthy individuals stratified by sex, age and body mass index (BMI). Our results provide, for the first time, an insight into the dynamics of adrenal steroids in tissue in real world settings and will serve as a normative reference for novel and improved biomarkers of endocrine disorders. (ULTRADIAN, NCT02934399).
Subject	Medicine, Health and Life Sciences
Keyword	Microdialysis (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Monitoring, Ambulatory (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Tandem Mass Spectrometry (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Adrenal Cortex Function Tests (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Biomedical Technology (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Ultradian Rhythm (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Circadian Rhythm (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Adrenal Gland Diseases (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Adrenal Cortex Hormones (MeSH) https://www.ncbi.nlm.nih.gov/mesh/ Hydroxycorticosteroids (MeSH) https://www.ncbi.nlm.nih.gov/mesh/
Related Publication	Upton TJ, Zavala E, Methlie P, Kämpe O, Tsagarakis S, Øksnes M, et al. High-resolution daily profiles of tissue adrenal steroids by portable automated collection. Science Translational Medicine. 2023;15(701):eadg8464. doi: 10.1126/scitranslmed.adg8464 https://doi.org/10.1126/scitranslmed.adg8464
Language	English
Producer	University of Bergen (UiB) https://www.uib.no/en
Funding Information	EU Horizon 2020: 633515
Distributor	University of Bergen (University of Bergen) https://dataverse.no/dataverse/uib
Depositor	Upton, Thomas
Deposit Date	2023-03-16
Date of Collection	Start Date: 2017-05-02 ; End Date: 2020-02-26
Data Type	Machine readable text files; clinical data
Software	Python, Version: 3.9 or later REDCap

Life Sciences Metadata

Design Type	Cohort Study
Measurement Type	Other
Other Measurement Type	Quantification of hormones in microdialysate and plasma
Technology Type	Other
Other Technology Type	LC-MS/MS; Microdialysis
Technology Platform	Xevo TQ-S (Waters)
Other Technology Platform	mDialysis 30mm linear probe [20kDa cutoff]; U-RHYTHM prototype microdialysis sampler

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